CAMBRIDGE, Mass. & CHICAGO, Jun 02, 2011 (BUSINESS WIRE) -- AVEO Pharmaceuticals, Inc. (NASDAQ: AVEO) today announced results from the Phase 1b portion of its Phase 1b/2 clinical study of ficlatuzumab in combination with gefitinib (Iressa(TM)) in Asian subjects with non-small cell lung cancer (NSCLC). Ficlatuzumab is AVEO's lead monoclonal antibody candidate and a potent HGF/c-MET pathway inhibitor, and these results show that ficlatuzumab was well tolerated and demonstrated clinical activity in patients with NSCLC when combined with gefitinib. The Phase 1b results as well as an update on the ongoing Phase 2 portion of the trial will be featured as poster presentations during the 47th Annual Meeting of the American Society of Clinical Oncology (ASCO), abstract numbers 7571 and TPS213 respectively.

Tony Mok, M.D., professor, Department of Clinical Oncology, The Chinese University of Hong Kong, and senior investigator of the Phase 1b/2 trial commented, "The Phase 1b data show that the combination of ficlatuzumab and gefitinib demonstrated promising clinical activity and was well tolerated in patients. These data are encouraging as we continue to evaluate ficlatuzumab in combination with gefitinib in patients with both wild-type and mutant EGFR NSCLC in the ongoing Phase 2 trial."

Overview of the Clinical Trial

This Phase 1b/2 clinical trial is designed to test the activity of ficlatuzumab in combination with gefitinib in first-line treatment of Asian subjects with NSCLC. During the Phase 1b portion, there was a dose escalation of ficlatuzumab (first cohort of three patients received 10 mg/kg and second cohort of twelve patients received 20 mg/kg intravenously every two weeks) in combination with gefitinib (250 mg once-daily, oral for full four week cycle) in 15 Asian patients with NSCLC. The objective was to determine the safety, tolerability, dose-limiting toxicity (DLT), and recommended dose of ficlatuzumab in combination with gefitinib for the Phase 2 portion (RP2D). All patients were pre-treated with chemotherapy and ten patients had prior treatment EGFR tyrosine kinase inhibitors (TKI). With a median duration of treatment of 14 weeks among patients in the RP2D cohort, key findings include:

The combination of ficlatuzumab and gefitinib was well tolerated and demonstrated clinical activity in patients with NSCLC

Out of the 12 patients in the RP2D cohort, five patients (all of whom had no prior EGFR TKI therapy) experienced a partial response and four patients experienced stable disease.

"These Phase 1b results demonstrate the combinability of ficlatuzumab with an established anti-cancer agent and suggest the potential for efficacy of such a combination in NSCLC, one of the most devastating and difficult to treat cancers," said Tuan Ha-Ngoc, president and chief executive officer of AVEO. "We are pleased to report we have recently completed patient enrollment in the ongoing Phase 2 portion of this trial evaluating ficlatuzumab in combination with gefitinib as first-line therapy for patients with wild-type and mutant EGFR NSCLC. We anticipate top-line data from the Phase 2 portion of the trial in 2012."

The Phase 2 portion of the study began after determination of the RP2D in the dose-escalating Phase 1b portion and in parallel with the Phase 1b safety expansion. The open-label, two-arm, randomized Phase 2 study is designed to compare the combination of ficlatuzumab and gefitinib versus gefitinib monotherapy, in clinically selected Asian subjects with previously untreated advanced NSCLC who have a high likelihood of harboring activating EGFR mutations. Subjects who demonstrate disease control (complete response, partial response, or stable disease for 12 weeks or longer) in the gefitinib alone arm will cross-over upon progression to a combination of gefitinib and ficlatuzumab to assess whether acquired resistance to gefitinib can be overcome with the addition of ficlatuzumab. Although molecular markers are not required for study entry, tumor tissue has been obtained from the majority of patients for biomarker and correlative studies.

About Ficlatuzumab and the HGF/c-MET Pathway

The HGF/c-MET pathway is believed to play an important role in regulating tumor growth, invasion and metastasis, making it an exciting novel target in oncology. HGF/c-MET over-expression is observed in many tumors including bladder, lung, breast, gastric, ovarian, prostate, colorectal, head and neck, certain sarcomas and several other solid tumors as well as hematologic malignancies. The HGF/c-MET pathway has only one known ligand (HGF) that binds to one known receptor (c-MET) to initiate signaling. In addition, industry research suggests that increased HGF and/or c-MET receptor amplification may confer resistance to EGFR inhibitors. Ficlatuzumab (AV-299), discovered by AVEO through its Human Response Platform(TM) (HRP), is a potent anti-HGF/c-MET antibody with high affinity for the HGF ligand.

In AVEO's proprietary tumor models with elevated HGF/c-MET signaling, ficlatuzumab exhibited strong additive anti-tumor effect when given in combination with other approved anti-cancer agents such as erlotinib (Tarceva®), cetuximab (Erbitux®) and temozolomide (Temodar®). In additional preclinical studies, ficlatuzumab was more effective at inhibiting tumor growth (at the dose tested) than other anti-HGF antibodies currently in clinical development.

Following successful completion of earlier clinical trials, AVEO initiated a Phase 1b/2 clinical trial evaluating ficlatuzumab in combination with gefitinib (Iressa(TM)) versus gefitinib monotherapy in patients with NSCLC. Top-line data from the ongoing Phase 2 portion of the trial are expected in 2012.

About AVEO

AVEO Pharmaceuticals (NASDAQ: AVEO) is a cancer therapeutics company committed to discovering, developing and commercializing targeted therapies to impact patients' lives. The company's lead product candidate, tivozanib, is currently being investigated in a global, randomized Phase 3 clinical trial called TIVO-1 comparing tivozanib to sorafenib in patients with advanced renal cell carcinoma, as well as additional clinical studies in other solid tumor types. AVEO's second most advanced product candidate, ficlatuzumab (AV-299), is a potent, functional anti-HGF/c-MET pathway antibody that is currently in Phase 2 clinical development. AVEO's proprietary Human Response Platform(TM) is designed to offer the company a unique advantage in cancer drug development and has provided a discovery engine for multiple therapeutic targets. This approach has resulted in a promising pipeline of monoclonal antibodies against novel targets including HGF, ErbB3, RON, Notch and FGFR. For more information, please visit the company's website at www.aveopharma.com.

Forward-looking Statements

Any statements in this press release about our future expectations, plans and prospects, including statements about: the potential tolerability and efficacy of ficlatuzumab; the potential combinability of ficlatuzumab with other anti-cancer agents; the expected timing of receipt of clinical data from the Phase 2 portion of the clinical trial of ficlatuzumab in combination with gefitinib; the potential of our antibody research and development capabilities; the potential of our cancer biology platform to offer a unique advantage in oncology drug development; and other statements containing the words "believes," "anticipates," "plans," "expects," "will" and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including risks relating to: our ability to successfully research, develop and obtain and maintain regulatory approvals for our product candidates; the possibility that favorable preclinical trial results may not be predictive of the results in future preclinical and clinical trials; our inability to obtain and maintain adequate protection for intellectual property rights relating to our product candidates and technologies; unplanned operating expenses; our inability to raise substantial additional funds to achieve our goals, including with respect to the further development of ficlatuzumab; competition; general economic and industry conditions; and other factors discussed in the "Risk Factors" section of our most recent Form 10-Q filed with the Securities and Exchange Commission, and in other filings that we periodically make with the SEC. In addition, the forward-looking statements included in this press release represent our views as of the date of this press release. We anticipate that subsequent events and developments will cause our views to change. However, while we may elect to update these forward-looking statements at some point in the future, we specifically disclaim any obligation to do so. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this press release.